Thoughts on a possible late breaker from me on SA
Posted: Sat Nov 11, 2017 9:17 pm
Consider the following:
1. MF trial initial internal reviewed 20 patients in each of one of two arms. Low dose arm terminated at 12 week mark. This translates into 11 doses of Imetelstat. So after 11 doses all patients allowed to transfer to high dose arm which continues. Primary internal pre determined end points not reached in either group and the study suspended enrollment but continued with existing patients.
2. We are 14 months since the study suspended (26 months since study inception and now about 100 patients enrolled but no idea how many are alive) and have not reached OS but no real look at OS will come until third quarter of next year or before if more patients fail to survive. Janssen and Geron seem in no hurry to share the OS data. In part I think because the data speaks for itself and exceeds current benchmarks anyway but may not yet be significant enough to warrant stopping the study.
3. The FDA is intimately familiar with Imetelstat since before the time of the halt through granting FT for MDS. And they have requested current data for in the MF population, presumably to consider accelerated approval status (this of course is pure conjecture but it gets better, or worse depending on your point of view--see 4.)
4. Dr. S has always sidestepped any mention of PR/CR/CI rates in the R/R study. Given that something stopped the 4.7 arm and facilitated the 9.4 arm with now 26 (max) months of data and given that Janssen/Geron does not want to or can't yet discuss OS in detail. I put forth a prediction that there is a modest chance for a late breaking abstract to discuss hematologic improvements (of all types) in this patient population who has never been systematically studied before on drug. They have enough data to present now, heck they had enough at eleven weeks to modify the study. The FDA has enough data to review and looked on the MDS data to date favorably. I submit that an MF abstract would be submitted as late as possible to emphasize durability of effect. There may not be a lot to be said for CRs and PRs as in front line but stable disease in a terminal population may be worth a late breaker. We will know on Nov 21st. Good luck to all and Best Regards, bp
1. MF trial initial internal reviewed 20 patients in each of one of two arms. Low dose arm terminated at 12 week mark. This translates into 11 doses of Imetelstat. So after 11 doses all patients allowed to transfer to high dose arm which continues. Primary internal pre determined end points not reached in either group and the study suspended enrollment but continued with existing patients.
2. We are 14 months since the study suspended (26 months since study inception and now about 100 patients enrolled but no idea how many are alive) and have not reached OS but no real look at OS will come until third quarter of next year or before if more patients fail to survive. Janssen and Geron seem in no hurry to share the OS data. In part I think because the data speaks for itself and exceeds current benchmarks anyway but may not yet be significant enough to warrant stopping the study.
3. The FDA is intimately familiar with Imetelstat since before the time of the halt through granting FT for MDS. And they have requested current data for in the MF population, presumably to consider accelerated approval status (this of course is pure conjecture but it gets better, or worse depending on your point of view--see 4.)
4. Dr. S has always sidestepped any mention of PR/CR/CI rates in the R/R study. Given that something stopped the 4.7 arm and facilitated the 9.4 arm with now 26 (max) months of data and given that Janssen/Geron does not want to or can't yet discuss OS in detail. I put forth a prediction that there is a modest chance for a late breaking abstract to discuss hematologic improvements (of all types) in this patient population who has never been systematically studied before on drug. They have enough data to present now, heck they had enough at eleven weeks to modify the study. The FDA has enough data to review and looked on the MDS data to date favorably. I submit that an MF abstract would be submitted as late as possible to emphasize durability of effect. There may not be a lot to be said for CRs and PRs as in front line but stable disease in a terminal population may be worth a late breaker. We will know on Nov 21st. Good luck to all and Best Regards, bp